Ksr-2 Lentiviral Activation Particles (h2): sc-402872-LAC-2

Human KSR2 (kinase suppressor of Ras 2) encodes Ksr-2, a scaffold/regulatory pseudokinase that organizes RAF–MEK–ERK signaling downstream of RAS to tune MAPK pathway amplitude, duration, and subcellular localization. Ksr-2 also integrates cellular energy and nutrient cues through interactions with AMPK-associated networks, linking growth-factor signaling to metabolic homeostasis, mitochondrial function, and adaptive responses to energy stress. Genetic and functional studies associate KSR2 perturbation with disorders of energy balance and neuroendocrine regulation, including severe obesity and insulin resistance, highlighting its role in coordinating signaling and metabolism. KSR2 gene-editing reagents enable mechanistic dissection of MAPK and AMPK crosstalk, pathway rewiring, and cell-type-specific regulation in relevant human cellular models.

Ksr-2 Lentiviral Activation Particles (h2) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient KSR2 upregulation across a broader range of human cell types.

Ksr-2 Lentiviral Activation Particles (h2) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the KSR2 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous Ksr-2 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native KSR2 genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.